DESCRIPTION (Adapted from the application): The long-term objective of the proposal is the design and synthesis of clinically useful antitumor agents that depend upon their interaction with specific nuclear proteins to produce their selective killing of cancer cells. Phases II and III will include compound synthesis, and preclinical and clinical trials in collaboration with the Institute for Drug Development, San Antonio. The specific aims of Phase I of this proposal are to: (1) design and synthesize molecules that upon covalent reaction with DNA release a concealed ligand; (2) demonstrate that covalent reaction with DNA is required to facilitate the release of the concealed ligand. A "trigger mechanism" that depends upon a DNA-dependent release of a concealed ligand is the key feature of this proposal. This will initiate a cascade of events, leading to the "hijacking" of nuclear proteins, which in turn can conceal the DNA adduct from repair mechanisms and give rise to selective toxicity in target cells or interfere with normal transcriptional control processes. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE